Alzheimer's Disease Research Using Human Microglia

被引:18
作者
Lue, Lih-Fen [1 ,2 ,3 ]
Beach, Thomas G. [1 ]
Walker, Douglas G. [2 ,3 ,4 ]
机构
[1] Banner Sun Hlth Res Inst, Sun City, AZ 85351 USA
[2] Arizona State Univ, Neurodegenerat Dis Res Ctr, Tempe, AZ 84027 USA
[3] Arizona State Univ, Sch Life Sci, Tempe, AZ 84027 USA
[4] Shiga Univ Med Sci, Mol Neurosci Res Ctr, Otsu, Shiga 520, Japan
关键词
neuroinflammation; microglia; cell culture; brain; amyloid; neurodegeneration; autopsy; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; PROGRANULIN POLYMORPHISM RS5848; PLASMINOGEN-ACTIVATOR RECEPTOR; PLURIPOTENT STEM-CELLS; ADULT HUMAN MICROGLIA; HUMAN BRAIN; HUMAN FETAL; MULTIPLE-SCLEROSIS; GENE-EXPRESSION;
D O I
10.3390/cells8080838
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Experimental studies of neuroinflammation in Alzheimer's disease (AD) have mostly investigated microglia, the brain-resident macrophages. This review focused on human microglia obtained at rapid autopsies. Studies employing methods to isolate and culture human brain microglia in high purity for experimental studies were discussed. These methods were employed to isolate human microglia for investigation of a number of features of neuroinflammation, including activation phenotypes, neurotoxicity, responses to abnormal aggregated proteins such as amyloid beta, phagocytosis, and the effects of aging and disease on microglia cellular properties. In recent years, interest in human microglia and neuroinflammation has been renewed due to the identification of inflammation-related AD genetic risk factors, in particular the triggering receptor expressed on myeloid cells (TREM)-2. Because of the difficulties in developing effective treatments for AD, there has been a general need for greater understanding of the functions of microglia in normal and AD brains. While most experimental studies on neuroinflammation have employed rodent microglia, this review considered the role of human microglia in experimental studies. This review focused on the development of in vitro methodology for the culture of postmortem human microglia and the key findings obtained from experimental studies with these cells.
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页数:19
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